DESCRIPTION: The generation, migration and differentiation of neurons is largely considered a developmental process that ends soon after birth. Recent studies have shown that adult mammalian CNS contains a population of dividing precursor cells in the subventricular zone (SVZ) of the lateral ventricles, which are capable of forming new neurons in vitro. The biological reasons for the permanence of neuronal precursor cells in the CNS of adult mammals is unknown. The experiments outlined in this proposal are designed to investigate in detail the fate of the proliferating SVZ cells in the adult mouse. Small patches of dividing SVZ cells will be labeled either with 3H-thymidine, DiI, or by transplantation of tissue from transgenic mice. The pathways of migration of labeled cells will be charted, and the mature phenotypic characteristics of neurons derived from the dividing population will be determined. In addition, the ultrastructure of dividing and mature, new cells will be examined. Transplantation of adult SVZ tissue into embryonic or neonatal hosts will be used to assess whether such heterochronic environments can induce SVZ cells from adults to form neurons that are normally produced only early in development. Finally, experimental strategies are presented to determine if adult SVZ cells can replace neurons damaged by lesions in the CNS. The characterization of the developmental potential of these stem cells in the adult mammalian CNS is an important first step in determining the potential use of these cells for brain repair following injury or disease.